Verghese C, DeLeon J, Nair C, Simpson G M
MCP/NSH Clinical Research Center, Norristown State Hospital, PA 19401, USA.
Biol Psychiatry. 1996 Jan 15;39(2):135-8. doi: 10.1016/0006-3223(95)00215-4.
Withdrawal effects of neuroleptics have not received much attention. Clozapine withdrawal phenomena have been attributed to psychosis arising from D2 supersensitivity, which is unlikely since it has minimal action on D2 receptors. The time course and clinical features of this phenomenon suggest that cholinergic overdrive and gamma-aminobutyric acid (GABA) supersensitivity occurs after withdrawal, since it is strongly anticholinergic and has a GABAergic action. Recently, a number of patients showed marked decompensation when they were switched from clozapine to risperidone, especially when they were rapidly tapered off clozapine. This was probably more due to withdrawal effects than the primary psychosis or a lack of efficacy of risperidone. A slow withdrawal schedule would facilitate homeostatic mechanisms; anticholinergics would be useful in clozapine withdrawal. This area has not received any attention from researchers, nor are there any guidelines for clinicians. This will be particularly important with the widespread use of atypical agents in the future.
抗精神病药物的撤药效应尚未得到太多关注。氯氮平撤药现象被归因于由D2超敏反应引起的精神病，但这种说法不太可能成立，因为它对D2受体的作用极小。该现象的时间进程和临床特征表明，撤药后会出现胆碱能亢进和γ-氨基丁酸（GABA）超敏反应，因为它具有强烈的抗胆碱能作用且有GABA能作用。最近，一些患者从氯氮平换用利培酮时出现明显失代偿，尤其是在快速停用氯氮平的情况下。这可能更多是由于撤药效应，而非原发性精神病或利培酮缺乏疗效。缓慢的撤药方案将有助于体内平衡机制；抗胆碱能药物在氯氮平撤药时会有用。这一领域尚未受到研究人员的任何关注，临床医生也没有相关指南。随着未来非典型药物的广泛使用，这将尤为重要。
